AUTHOR=Wang Zeyu , Dai Ziyu , Zhang Hao , Liang Xisong , Zhang Xun , Wen Zhipeng , Luo Peng , Zhang Jian , Liu Zaoqu , Zhang Mingyu , Cheng Quan 
  
TITLE=Tumor-secreted lactate contributes to an immunosuppressive microenvironment and affects CD8 T-cell infiltration in glioblastoma
  
JOURNAL=Frontiers in Immunology
  
VOLUME=Volume 14 - 2023
  
YEAR=2023
  
URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.894853
  
DOI=10.3389/fimmu.2023.894853
  
ISSN=1664-3224
  
ABSTRACT=Glioblastoma is a malignant brain tumor with poor prognosis. Lactate is the main product of tumor cells and its secretion may relate to immunocytes’ activation. However, its role in glioblastoma is poorly understood. Therefore, this work aimed at exploring their connections with bulk RNA-seq analysis and single cell RNA-seq analysis. Over 1400 glioblastoma samples were grouped into different clusters according to their expression and the results were validated with our own data. Lactate level can predict glioblastoma progression and modulate tumor immune landscape. Furthermore, machine learning algorithms and cell-cell interaction implied that CD8 T cells and microglial cells may actively communicate with tumor through lactate. In the meantime, by co-culturing CD8 T cells and tumor cells, and immunohistochemistry on Xiangya cohort samples supported that CD8 T cells’ proliferation and infiltration ratio are inhibited in high lactate microenvironment. Interestingly, samples with different lactate secretion ability may also response to interferon-gamma differently, and the expression of immune escape associated genes is also dysregulated. Together those results implied that lactate contribute to glioblastoma immune suppressive microenvironment. Moreover, potential compounds were also predicted based on the cluster model which may offer novel treatments. Generally, tumor secreted lactate can promote glioblastoma progression by influencing CD8 T cells and tumor response to interferon-gamma.